CAR-T Therapy for Non-Hodgkin's Lymphoma

Recruiting at 29 trial locations

Overseen By Study Contact, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: Anti-CD20 antibody

Disqualifiers: Organ transplant, Stroke, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

230 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment where a patient's own immune cells are modified to better attack their cancer. It is for adults with a type of lymphoma that hasn't responded to other treatments. The modified cells target specific proteins on the cancer cells to help the immune system destroy them. This new method enhances the patient's immune cells to find and eliminate cancer cells.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment C-CAR039 for Non-Hodgkin's Lymphoma?

The effectiveness of C-CAR039, a CAR-T therapy, can be indirectly supported by studies on similar treatments like axicabtagene ciloleucel and tisagenlecleucel, which have shown promising results in treating relapsed or refractory large B-cell lymphoma, a type of Non-Hodgkin's Lymphoma. These therapies have demonstrated durable responses in patients who had limited options, suggesting potential benefits for C-CAR039 as well. ^{1 2 3 4 5}

What safety data exists for CAR-T therapy in humans?

CAR T-cell therapies, like those targeting CD19 for non-Hodgkin lymphoma, can cause side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which may affect the brain and nervous system. These side effects are known complications and require careful management. ^{6 7 8 9 10}

What makes the treatment C-CAR039 unique for Non-Hodgkin's Lymphoma?

C-CAR039 is a novel CAR-T cell therapy that targets both CD19 and CD20 proteins on B-cells, unlike other CAR-T therapies that typically target only CD19. This dual targeting may enhance its effectiveness in treating Non-Hodgkin's Lymphoma by potentially overcoming resistance seen in single-target therapies. ^{1 11 12 13 14}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Adults with B-Cell non-Hodgkin lymphoma that has come back or didn't respond after at least two standard treatments can join. They must be over 18, have a certain level of physical fitness (ECOG status 0 or 1), and their major organs need to function well. People with recent serious blood clots, active severe infections, other cancers within the last five years (except some skin or in situ cancers), pregnant women, and those with certain heart conditions cannot participate.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My tumor is confirmed to be CD19 or CD20 positive.

I have been diagnosed with a type of aggressive large B cell lymphoma or follicular lymphoma.

Exclusion Criteria

I had a blood clot in my leg or lung in the last 6 months.

I had a stem cell transplant less than 12 weeks before my CAR T cell treatment.

I have been diagnosed with a specific type of lymphoma linked to the HHV-8 virus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intravenous infusion of autologous JNJ-90014496 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and pharmacokinetics after treatment

24 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

3 years

Treatment Details

Interventions

• C-CAR039

Trial Overview The trial is testing JNJ-90014496, an experimental CAR T-cell therapy targeting CD19 and CD20 proteins on cancer cells. It's for adults whose aggressive B-cell non-Hodgkin lymphoma hasn't been cured by previous treatments. This Phase Ib study is open-label, meaning everyone knows they're getting the test treatment.

Participant Groups

Group I: JNJ-90014496 Experimental Treatment 1 Intervention

Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1.

C-CAR039 is already approved in United States, China for the following indications:

Approved in United States as C-CAR039 for:

• Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)
• Follicular lymphoma

Approved in China as C-CAR039 for:

• Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Cellular Biomedicine Group Ltd.

Lead Sponsor

Trials

32

Recruited

1,600+

Cellular Biomedicine Group, Inc.

Lead Sponsor

Trials

3

Recruited

270+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

Findings from Research

In the RELIANCE study involving 68 patients with heavily pre-treated relapsed/refractory large B-cell lymphoma, relmacabtagene autoleucel (relma-cel) showed a high objective response rate of 77.59% and a complete response rate of 53.45% after a median follow-up of 17.9 months.

The treatment demonstrated a manageable safety profile, with only 5.1% of patients experiencing severe cytokine release syndrome and 3.4% experiencing severe neurotoxicity, indicating that relma-cel is both effective and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. Ying, Z., Yang, H., Guo, Y., et al.[2023]

In a phase 2 trial involving 153 patients with relapsed or refractory indolent non-Hodgkin lymphoma, axicabtagene ciloleucel CAR T-cell therapy demonstrated a high overall response rate of 92%, with 74% achieving a complete response, indicating its efficacy in this patient population.

The treatment had a manageable safety profile, with the most common severe adverse events being cytopenias and infections, and only 3% of patients experiencing treatment-related deaths, suggesting that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Jacobson, CA., Chavez, JC., Sehgal, AR., et al.[2022]

In the phase II JULIET trial, the CAR T-cell therapy tisagenlecleucel targeting CD19 demonstrated durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma, with 32% achieving complete responses at 3 months.

The efficacy remained stable at 6 months, with 30% of patients still showing complete responses, indicating the potential long-term effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

In a phase II study involving 45 chemotherapy-naive patients with carcinoma of unknown primary site (CUP), the combination of irinotecan and carboplatin showed an objective response rate of 41.9%, indicating significant efficacy in treating this rare cancer.

The treatment resulted in a median survival of 12.2 months, with manageable but notable side effects, including neutropaenia and leukopaenia, suggesting that this regimen could be a viable option for patients with CUP who have a good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus carboplatin for patients with carcinoma of unknown primary site. Yonemori, K., Ando, M., Yunokawa, M., et al.[2023]

Axicabtagene ciloleucel and tisagenlecleucel are effective CAR T-cell therapies targeting CD19 for treating B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma, but they can lead to serious complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

ICANS can occur alongside CRS and may affect the central nervous system due to elevated cytokine levels, but there is currently no consensus on the best management strategies for this condition, highlighting the need for improved identification and treatment protocols in intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. Rivera, AM., May, S., Lei, M., et al.[2021]

In a phase II study involving 29 patients with refractory or relapsed small cell lung cancer, the combination of irinotecan (CPT-11) and carboplatin showed a 31% overall response rate, indicating it can be an effective second-line treatment option.

While the treatment demonstrated activity, it also had significant toxicity, with 52% of patients experiencing severe neutropenia and one treatment-related death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. Naka, N., Kawahara, M., Okishio, K., et al.[2019]

In a study of 28 patients with platinum-resistant recurrent ovarian cancer, combination therapy with irinotecan and platinum showed a 14% overall response rate, with a clinical benefit rate of 68% when including stable disease.

While the treatment was associated with significant adverse events, particularly hematological issues in 68% of patients, these were manageable, suggesting that CPT-Pt could be a viable option for patients in this challenging clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series. Shibutani, T., Takano, M., Miyamoto, M., et al.[2020]

In a study involving 9 patients with cervical cancer, combination therapy using irinotecan and nedaplatin showed a 40% response rate in patients receiving treatment before surgery and a 75% response rate in those with recurrent disease.

While the treatment was effective, it also led to significant side effects, including grade 3 or 4 adverse events such as leukopenia in 4 patients, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. Hiruma, R., Kamide, T., Anzai, N., et al.[2018]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

Tisagenlecleucel and axicabtagene ciloleucel are groundbreaking CAR-T cell therapies that have shown high effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of B-cell non-Hodgkin lymphomas.

This review highlights the challenges faced by physicians in administering these therapies and discusses future directions for research and treatment in the field of immune and cellular therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Mohty, M., Gautier, J., Malard, F., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy, specifically anti-CD19 CAR T-cell therapies like axicabtagene ciloleucel and tisagenlecleucel, have been approved for treating relapsed or refractory aggressive B-cell lymphoma, marking a significant advancement after decades of limited treatment options.

These therapies have shown promising efficacy in clinical trials, but they also come with potential toxicities, highlighting the need for ongoing research to enhance their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of CAR T-cell therapy in aggressive B-cell lymphoma. Nair, R., Neelapu, SS.[2021]

In a pivotal phase 2 study involving 93 adult patients with relapsed or refractory diffuse large B-cell lymphoma, CAR T-cell therapy with tisagenlecleucel achieved a best overall response rate of 52%, with 40% of patients experiencing complete responses.

The treatment demonstrated durable responses, with a 12-month relapse-free survival rate of 65%, and no deaths were attributed to the therapy itself, although some patients experienced significant adverse events like cytokine release syndrome and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Schuster, SJ., Bishop, MR., Tam, CS., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Irinotecan plus carboplatin for patients with carcinoma of unknown primary site. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]

12. England pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

The promise of CAR T-cell therapy in aggressive B-cell lymphoma. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2019]